期刊
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
卷 74, 期 22-24, 页码 1493-1503出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15287394.2011.618978
关键词
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资金
- National Institutes of Health (NIH) [R01 NS062787]
- CJD Foundation
- Alliance BioSecure
- University Center on Aging and Health
- McGregor Foundation
- Case Western Reserve University
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS062787] Funding Source: NIH RePORTER
Prion diseases are a group of incurable transmissible neurodegenerative disorders. The key molecular event in the pathogenesis of prion diseases is the conversion of the cellular prion protein (PrPC) into its pathological isoform (PrPSc), accompanied by a conformational transition of alpha-helix into beta-sheet structure involving the structured alpha-helix 1 domain from residues 144-154 of the protein (PrP144-154). Blocking the accessibility of PrP144-152 with anti-PrP antibody 6H4 was found to prevent PrP conversion and even to cure prion infection in cell models (Enari et al. 2001). Previously, Yuan et al. (2005) demonstrated that the reduction and alkylation of PrP induced concealment of the 6H4 epitope. This study examined the ability of mechlorethamine (MCT), an alkylating antitumor drug, to conceal the 6H4 epitope and block PrP conversion in the presence of a reducing reagent. Mechlorethamine treatment significantly decreased in vitro amplification of PrPSc in the highly efficient protein misfolding cyclic amplification system. Our findings suggest that MCT may serve as a potential therapeutic agent for prion diseases.
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